Cantilever sensors can be broadly divided into two categories, depending upon dimensions of the sensor: micro-cantilevers and macro-cantilevers. Micro-cantilever sensors can be utilized in both static (bending) mode and dynamic (resonance) mode. In static mode, the deformation of the cantilever arm is measured to determine if an analyte (substance under analysis) is present. In dynamic mode, a resonance frequency is measured to determine if an analyte is present. Macro-cantilever sensors typically are not utilized in the static mode because bending of the cantilever arm is often limited. Macro-cantilever sensors can be utilized under liquid immersion conditions or in a gas or vacuum. Typically, greater sensitivity is achievable when a cantilever sensor is utilized in a gas/vacuum than in a liquid. Liquid dampening tends to adversely affect sensitivity. However, measuring analytes in liquid medium has many practical applications.
One type of known micro-cantilever sensor is a silicon-based micro-cantilever sensor. A typical silicon-based micro-cantilever sensor comprises a micro-cantilever that acts as a resonator. The micro-cantilever is driven by an external actuator at the base of the micro-cantilever to generate vibrations in the resonator. Typically, the vibrations are detected by an external optical detector. One disadvantage of typical silicon-based micro-cantilevers is the complex external optical components required for detection. Further, optical detection means disadvantageously limit application of the micro-cantilever sensor to optically clear samples. Another disadvantage is the weight and complexity added to the sensor due to the external actuator. Yet another disadvantage is that the external actuator can be located only at the base of the micro-cantilever, which limits its effectiveness in driving the cantilever's vibration. A further disadvantage of silicon-based micro-cantilever sensors is that they are mechanically fragile. Thus, silicon-based micro-cantilever sensors can not be used in high liquid flow rate environments. Further, typical silicon-based micro-cantilever sensors lose detection sensitivity in liquid media due to viscous damping.
Another type of known cantilever sensor is a quartz-based piezoelectric cantilever sensor. Quartz is a weak piezoelectric, and thus, much like silicon-based cantilever sensors, quartz-based piezoelectric cantilever sensors lose detection sensitivity in liquid media due to viscous damping. Further, the detection sensitivity of quartz-based sensors is limited by the planar geometry of the sensor.
Conventional piezoelectric cantilevers are known to be fabricated with a piezoelectric layer attached to a non-piezoelectric layer over part or the entire surface of the piezoelectric layer. In some conventional piezoelectric cantilevers, the piezoelectric layer is fixed at one end so that when the piezoelectric material is excited, the non-piezoelectric layer flexes to accommodate the strain caused in the piezoelectric material. When the frequency of excitation is the same as the natural frequency of the underlying mechanical structure, resonance occurs. This type of piezoelectric cantilever sensor is known to operate at frequencies lower than about 100 kHz at millimeter size. Currently, higher frequencies are obtainable only by making the cantilever sensor very short (less than 1.0 mm in length), very narrow (less than 0.1 mm in width), and very thin (less than 100 microns in thickness). However, reducing the dimensions of the cantilever sensor, particularly the width, thusly, makes the cantilever sensor less usable in a liquid medium due to viscous damping. Damping increases inversely with square of cantilever width.
Most current bio-sensing technologies rely on fluorescence, lasers, fiber-optics-based methods, quartz crystal microbalance technology, electrochemical enzyme immunoassays, and/or binding to metal particles. Most of these techniques are neither direct, nor quantitative. Many of these techniques are also quite slow. In addition, most of the aforementioned techniques do not lend themselves to measurement of changes in mass, which may provide a convenient way to measure a variety of different parameters.
A mass sensor based on resonance frequency requires three components, an actuator (driver), a resonator, and a detector. One example of a mass sensor is a silicon-based micro-cantilever, which can be easily integrated with existing silicon based methodologies. In a silicon-based micro-cantilever mass sensor, the micro-cantilever acts as the resonator and is driven by an external lead zirconate titanate (PZT) actuator at the base of the micro-cantilever to generate vibrations in the resonator, which may be detected by an external optical detector. For bio-detection, receptors are immobilized on the cantilever surface. Binding of antigens to the receptors immobilized on the cantilever surface increases the cantilever mass and causes a decrease in the resonance frequency. Detection of target molecules is achieved by monitoring the mechanical resonance frequency. In spite of the popularity of silicon-based micro-cantilevers, they rely on complex external optical components for detection. In addition, the PZT vibration driver adds to the weight and complexity of the sensor. Further, the external actuator can only be located at the base of the micro-cantilever, which greatly limits its effectiveness in driving the cantilever's vibration. The optical detection means also limits the application to optically clear samples.
In addition to mass detection, silicon-based micro-cantilevers have also been used as sensors for small molecules by detecting the stress generated on the cantilever by the adsorption of species onto receptors associated with the cantilever. Antibody or DNA receptors are coated on the surface of the micro-cantilevers to bind target biological molecules. The stress generated at the time of binding or unbinding of the target molecules to the receptors on the micro-cantilever surface induces a deflection of the micro-cantilever that may be detected by external optical components or by an adsorption-stress-induced DC voltage on a piezo-resistive coating layer on the cantilever surface.
Compared to silicon-based sensors, piezoelectric millimeter-sized cantilever sensors are not as bulky and complex. Piezoelectric devices are excellent transduction candidates because of their short response times and high piezoelectric coefficients. Because they are piezoelectric, both the driving and sensing of the mechanical resonance can be conveniently done electrically within the resonator. Currently, piezoelectric biosensors are based on commercially available quartz crystal microbalances (QCM), a disk device that uses thickness-mode resonance for sensing. Although quartz is a weak piezoelectric material, it is widely used as a layer thickness monitor in part due to the availability of large quartz single crystals to make the membranes. The typical mass detection sensitivity of a 5 MHz QCM that has a minimum detectable mass density (DMD) of 10−9 g/cm2 is about 10−8 g/Hz, about four orders of magnitude less sensitive than millimeter sized piezoelectric cantilevers.
Microcantilevers exist that are about 100 microns length, a few tens of microns wide, and a few microns thick. Such microcantilevers are used in bending or in resonance mode for detection. The disadvantage of these microcantilevers is that their resonance characteristics are very strongly diminished due to viscous damping. Further, their use in liquid media has been accomplished at very low flow rates of microliters/min.
D. W. Carr and H. G. Craighead, “Fabrication of nanoelectromechanical systems in single crystal silicon using silicon on insulator substrates and electron beam lithography,” J. vac. Sci. Technology. B., 15(6), 1997. pp 2760-2763, discloses the fabrication of beam sensors and multiple beam sensors in a mesh configuration of the order of a few hundred nanometers, and have achieved high resonant frequencies of 40 MHz. Copending U.S. application Ser. No. 11/659,919, filed Jan. 23, 2007, entitled, “Self-Exciting, Self-Sensing Piezoelectric Cantilever Sensor” was co-invented by the present inventor and discusses the architecture and basic operation of millimeter sized piezoelectric-excited cantilever sensors in a liquid sample environment.
Therefore, there exists a need to improve the sensing capabilities of existing sensors and a need for the provision of sensors with an improved ability to perform detection of airborne species.